Replies to post #34509 on NorthWest Biotherapeutics Inc (NWBO)

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I also found his article very interesting. The fact that he worked for Amgen, and didn't disclose that until after I'd revealed it was also very interesting to me.

I didn't find his opinion on DCVax to be very legitimate, however.

I did find Linda's comments regarding his blog to be especially pertinent...

22:04

Now let’s pause for just a moment and just quantify that a little bit. I think there’s been a lot of misunderstanding in the investor community about the extent of diversity of tumors… the point I’ve been emphasizing here this afternoon.

Just as one example, earlier this week there was a blog published saying that there were only there mutations, three differences, between patients with brain cancer, and patients with normal brain tissue cells.

The publication [not the blog, but an abstract] that was cited in that actually said no such thing. It said there were hundreds of mutations. But very importantly, that was a 2008 paper by a major consortium of two dozen major institutions mapping the cancer genome atlas.

MK's 2008 paper link
http://www.nature.com/nature/journal/v455/n7216/full/nature07385.html
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
October 23, 2008

Linda continued...

And that same research consortium of all these leading academic institutions published another paper five years more recently in October of 2013 in which they profiled two hundred ninety one glioblastoma patients, and they found twenty one thousand five hundred and forty [21,540] mutations. Not three mutations. Not differences from normal brain tumor tissue, but twenty one thousand differences.

Here's the link to the paper she referenced.

http://www.sciencedirect.com/science/article/pii/S0092867413012087 The Somatic Genomic Landscape of Glioblstoma
October 10, 2013

Whole-exome sequencing identifies significantly mutated genes in glioblastomas
Solution-phase hybrid capture and whole-exome sequencing were performed on paired tumor and normal native genomic DNA obtained from 291 patients. Overall, 138-fold mean target coverage was achieved, with 92% of bases covered at least 14-fold in the tumor and 8-fold in the normal – the threshold which offers 80% power to detect mutations with an allelic fraction of 0.3 (Carter et al., 2012) (see Extended Experimental Procedures). Overall, of the 291 tumor exomes sequenced, 21,540 somatic mutations were identified, with a median rate of 2.2 coding mutations per megabase (lower-upper quartile range: 1.8 – 2.3). Among the somatic mutations were 20,448 single nucleotide variants (SNVs), 39 dinucleotide mutations and 1,153 small insertions and deletions (indels). The SNVs mutations included 5,379 silent, 3,901 missense, 831 nonsense, 360 splice-site and 760 mutations resulting in a frame shift.

As far as the paper MK referenced in his parting comment that you provided the link for. I agree... there is very useful information there.
http://1.usa.gov/1ElD8eZ

First there is this...

There is a need for personalized strategies for cancer therapy that are compatible with mutational heterogeneity, and in this regard, immune interventions that aim to initiate or enhance anti-tumor immune responses hold much promise.

Then there is this...

There is a robust association between T cell infiltration of solid tumors and favorable patient outcomes.

And finally I thought this was interesting too...

While MK references figure one stating

Here is another, more current publication demonstrating that GBM, on a per patient basis, has a mutation rate in the low single digits (Figure 1):

The article later stated this...

The 16 brain tumor patients were excluded from the analysis as they were missing tumor stage information.

Any thoughts on that?